Measuring what matters to rare disease patients \u2013 reflections on the work by the IRDiRC taskforce on patient-centered outcome measures

Thomas Morel,Stefan J Cano

doi:10.1186/s13023-017-0718-x

Abstract

Our ability to evaluate outcomes which genuinely reflect patients’ unmet needs, hopes and concerns is of pivotal importance. However, much current clinical research and practice falls short of this objective by selecting outcome measures which do not capture patient value to the fullest. In this Opinion, we discuss Patient-Centered Outcomes Measures (PCOMs), which have the potential to systematically incorporate patient perspectives to measure those outcomes that matter most to patients. We argue for greater multi-stakeholder collaboration to develop PCOMs, with rare disease patients and families at the center. Beyond advancing the science of patient input, PCOMs are powerful tools to translate care or observed treatment benefit into an ‘interpretable’ measure of patient benefit, and thereby help demonstrate clinical effectiveness. We propose mixed methods psychometric research as the best route to deliver fit-for-purpose PCOMs in rare diseases, as this methodology brings together qualitative and quantitative research methods in tandem with the explicit aim to efficiently utilise data from small samples. And, whether one opts to develop a brand-new PCOM or to select or adapt an existing outcome measure for use in a rare disease, the anchors remain the same: patients, their daily experience of the rare disease, their preferences, core concepts and values. Ultimately, existing value frameworks, registries, and outcomes-based contracts largely fall short of consistently measuring the full range of outcomes that matter to patients. We argue that greater use of PCOMs in rare diseases would enable a fast track to Patient-Centered Care.

Highlights

Rare disease patients are increasingly confronted with a multi-faceted paradox.First, despite growing acceptance that patients have the clearest view of the health outcomes that matter, the success of the majority of rare disease drug development programmes rests on surrogate outcomes that may not reflect treatment benefits that patients value [1]
Despite growing acceptance that patients have the clearest view of the health outcomes that matter, the success of the majority of rare disease drug development programmes rests on surrogate outcomes that may not reflect treatment benefits that patients value [1]
Whilst patients’ plea for new treatments was duly heard and resulted in worldwide efforts to accelerate and intensify rare disease research, the regulatory approval and the critically important reimbursement of new treatments for rare diseases are increasingly difficult to obtain

Summary

Background

Rare disease patients are increasingly confronted with a multi-faceted paradox. First, despite growing acceptance that patients have the clearest view of the health outcomes that matter, the success (or failure) of the majority of rare disease drug development programmes rests on surrogate outcomes (e.g. laboratory measures, organ size) that may not reflect treatment benefits that patients value [1]. Whilst patients’ plea for new treatments was duly heard and resulted in worldwide efforts to accelerate and intensify rare disease research (as attested by the increase in orphan designations granted by regulatory agencies [2,3,4]), the regulatory approval and the critically important reimbursement of new treatments for rare diseases are increasingly difficult to obtain This is due, in part, to the lack of demonstration of improvement in meaningful health outcomes for patients. By either directly measuring patients’ clinical function or complementing the use of surrogates [Table 1], PCOMs offer the opportunity of a more meaningful and interpretable measure of patient benefit – thereby reducing uncertainty over treatment/ care effectiveness Their use is not limited to clinical studies investigating new drugs and extends to real-life clinical practice (including disease registries) to improve our understanding of the natural course of disease and guide treatment choices (notably through clinical guidelines and regulatory drug labeling). As ruxolitinib was being developed, its sponsor chose – after sustained interactions with the U.S FDA – to supplement the Phase 3 study primary endpoint on the reduction in spleen size with a newly-developed disease-specific patient-reported outcome (PRO) questionnaire (MSAF)

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